Difference between revisions of "On-Off Direction-Selective Ganglion Cell"

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[[File:onoffdsgc.png|thumb|right|400px|Reconstructed by [[Omni Desktop]] from Helmstaedter's skeleton]]
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[[File:MC36.jpeg|thumb|right|400px|an ON-OFF direction-selective ganglion cell reconstructed in EyeWire]]
  
Direction selective (DS) cells in the retina are defined as neurons that respond differentially to the direction of a visual stimulus. The term is used to describe a group of neurons that "gives a vigorous discharge of impulses when a (bright) stimulus object is moved through its receptive field in one direction" <ref name="barlow1965">{{cite journal  | author=H. B. Barlow and W. R. Levick|title=The Mechanism of Directionally Selective Units in Rabbit's Retina |journal=J. Physiol. |volume=178|pages=477-504 |year=1965}} [http://jp.physoc.org/content/178/3/477.full.pdf (PDF Download)]</ref>. There are three known types of DS cells in the vertebrate retina of the mouse, ON/OFF DS ganglion cells, ON DS ganglion cells, and OFF DS ganglion cells. Each has a distinctive physiology and anatomy<ref>"Motion Sensing in Vision." Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/wiki/Motion_Sensing_in_Vision (Accessed April 02, 2012).</ref>. The rest of this page will only apply to ON/OFF DS Ganglion Cells. There are also [[ON DS Ganglion Cells]] (which respond to the leading edge of a bright stimulus) and [[OFF DS Ganglion Cells]] (which respond only to the trailing edge of a bright stimulus).
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Direction selective (DS) cells in the retina are neurons that respond differentially to the direction of a visual stimulus. The term is used to describe a group of neurons that preferentially "gives a vigorous discharge of impulses when a stimulus is moved through its receptive field in one direction." <ref name="barlow1965">H. B. Barlow and W. R. Levick (1965) [http://jp.physoc.org/content/178/3/477.full.pdf The Mechanism of Directionally Selective Units in Rabbit's Retina] J. Physiol. <strong>178</strong>: 477-504</ref> There are three known types of DS cells in the vertebrate retina of the mouse, ON/OFF DS [[Ganglion Cell|Ganglion Cells]], ON DS Ganglion Cells (which respond to the leading edge of a bright stimulus) and OFF DS Ganglion Cells (which respond only to the trailing edge of a bright stimulus). Each has a distinctive physiology and anatomy.<ref name="wiki">"Motion Sensing in Vision." Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/wiki/Motion_Sensing_in_Vision (Accessed April 02, 2012).</ref> The rest of this page will only apply to ON/OFF DS Ganglion Cells.
 
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== Physiology ==
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== Physiology == <!--T:2-->
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[[File:ONOFFDCSG1.jpg|thumb|right|600px|Diagram showing the response of ON/OFF DSGC to stimulus in the null and preferred direction. Inputs are multiplied in the preferred direction, and suppressed in the null direction.<ref name = "vaney2011">D. I. Vaney, B. Sivyer, and W. R. Taylor (2012). Direction selectivity in the retina: symmetry and asymmetry in structure and function. Nature Neuroscience <strong>13</strong> (3): 194-208</ref>]]
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ON/OFF DSGCs act as local motion detectors. If a bright stimulus (e.g., a light) is moving in the direction of the cell's preference, the cell will fire at both the leading and trailing edge. An important contrast is that bright stimuli moving opposite the preferred direction (called the null direction), elicit little or no response <ref name="wiki" />.  The response to stimulus is independent of many stimulus properties, including size, shape, color, and speed.
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These cells have a center-surround structure, and the size of the [[Dendrite|dendrite]] correlates with the size of the center receptive field. <ref name="barlow1965" />
  
ON/OFF DS ganglion cells act as local motion detectors. They fire at the onset and offset of a bright stimulus (a light source). If a stimulus is moving in the direction of the cell’s preference, it will fire at the leading and the trailing edge.
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The classical receptive field of the ON–OFF DSGC exhibits center-surround structure, with the size of the receptive field center matching well with its dendritic diameter [6–8]. When presented with a moving bar visual stimulus, both the ON and OFF components of the spike response are direction-selective over a wide range of movement velocities <ref name="barlow1965" />. Furthermore, motion stimuli restricted to a small fraction (<20% in rabbit) of the receptive field can produce directional spiking of ON–OFF DSGCs, indicating that direction-selective mechanisms are present in local dendritic computational subunits that repeat in an array over the DSGC dendritic arbor <ref name="wei2011">{{cite journal  | author=W. Wei and M. B. Feller|title=€œOrganization and development of direction-selective circuits in the retina |journal=Trends Neurosci.|volume=34|issue=12|pages=638–645 |year=2011 |doi=10.1016/j.tins.2011.08.002}} [[media:10.1016_j.tins.2011.08.002.pdf|(PDF Download)]]</ref>.
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ON/OFF DSGCs can be divided into 4 subtypes differing in their directional preference, ventral, dorsal, nasal, or temporal. The cells of different subtypes also differ in their dendritic structure and synaptic targets in the brain.<ref name="kay2011" />
  
The direction in which a set of neurons respond most strongly to is their “preferred direction.” In contrast, they do not respond at all to the opposite direction, “null direction.” The preferred direction is not dependent on the stimulus- that is, regardless of the stimulus’ size, shape, or color, the neurons respond when it is moving in their preferred direction, and do not respond if it is moving in the null direction.
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From the early experiments in the 1960s, it was shown that receptive fields are fairly large, sensitive to small changes, and direction-selective subunits are repeated many times throughout the retina.<ref name="barlow1965" />
  
ON/OFF DS ganglion cells can be divided into 4 subtypes differing in their directional preference, ventral, dorsal, nasal, or temporal. The cells of different subtypes also differ in their dendritic structure and synaptic targets in the brain. The neurons that were identified to prefer ventral motion were also found to have dendritic projections in the ventral direction.
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== Anatomy == <!--T:5-->
  
Moving visual stimuli that crossed the cell’s receptive field elicited strong spiking when moving in a particular ‘preferred’ direction but little or no response when moving in the opposite ‘null’ direction.
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[[Image:DSGC_overview.jpg|thumb|Left|350px|Image of an On-Off Direction-Selective Ganglion Cell<ref name="borst2011">A. Borst and T. Euler (2011). €œSeeing Things in Motion: Models, Circuits, and Mechanisms. Neuron <strong>71</strong> (6): 974-994 doi:[http://dx.doi.org/10.1016/j.neuron.2011.08.031 10.1016/j.neuron.2011.08.031]</ref>.]]
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The ON/OFF DSGCs are commonly recognized by their bistratified dendritic arbors, which extend to two layers of the inner plexiform layer (IPL).  These cell types are also known to synapse with both [[Bipolar Cell|bipolar cells]] and [[Starburst Amacrine Cell|starburst amacrine cells (SAC)]].  As described above, there are four cell subtypes, each with own preference for direction.  Each subtype of ON/OFF DSGCs has differences in dendritic patterns and [[Axon|axonal projections]] to the brain. These differences indicate that outputs from different subtypes may wire to different parts of the brain <ref name="kay2011" />
  
[[Image:DSGC_orientation.jpg|500px]]
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[[Image:e2198_reconstruction.png|thumb|none|320px|Depiction of six reconstructed ON/OFFDSGCs.  Figure A shows the bistratification of the ON and OFF arbors.  Colors correspond to orientation of preferred direction.  Figure B shows a bottom view of the traced arbors.<ref name="briggman2011">K. L. Briggman, M. Helmstaedter, and W. Denk (2011).  [http://www.nature.com/nature/journal/v471/n7337/full/nature09818.html Wiring specificity in the direction-selectivity circuit of the retina Nature] <strong>471</strong>: 183–188</ref>]]
  
===Visual response properties===
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==Connections== <!--T:8-->
===Cellular biophysics===
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Excitation comes from both bipolar cells and starburst amacrine cells.<ref name="borst2011" /> The main source of inhibition is from starburst amacrine cells. Using manual reconstruction of 6 ON/OFF DSGCs and their synaptic partners, it was found that over 90% of SAC – ON/OFF DSGC synapses were oriented in the null direction.<ref name="briggman2011" />
  
== Anatomy ==
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As illustrated in the accompanying figure, light enters the retina through the photoreceptors, and excitatory inputs are transmitted to the ON/OFF DSGCs via Glutamate and Acetylcholine from the bipolar and starburst amacrine cells. Inhibitory GABA inputs, which are crucial for suppressing information in the null direction (and thereby creating a direction-selective motion detector) are received from SACs. The motion detection result is fed to higher parts of the brain for further processing.
The anatomy of ON/OFF cells is such that the dendrites extend to two sublaminae of the inner plexiform layer and make synapses with bipolar and amacrine cells. They have four subtypes, each with own preference for direction.
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The colored objects in panel a are six DSGCs reconstructed by the researchers. The circles are representations of the cell bodies, and the lines are "skeletons" of the dendrites. Each DSGC is said to be "bistratified," which means that its dendrites branch out in two sublayers ("strata") of the IPL. The total number of strata in the IPL is estimated to be around ten. A view of the bottom of the sandwich (panel b) shows the branching of the DSGC dendrites.
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[[Image:e2198_reconstruction.png|320px|Reconstructed ganglion and amacrine cells.]]
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===Location===
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===Shape===
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[[Image:DSGC_overview.jpg|thumb|none|350px|Image of an On-Off Direction-Selective Ganglion Cell<ref name="borst2011">{{cite journal  | author=A. Borst and T. Euler|title=€œSeeing Things in Motion: Models, Circuits, and Mechanisms |journal=Neuron |volume=71|issue=6|pages=974-994 |year=2011 |doi=10.1016/j.neuron.2011.08.031}} [[media:10.1016_j.neuron.2011.08.031.pdf|(PDF Download)]]</ref>.]]
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===Connections===
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[[File:DSGC_Brigmann.jpg|thumb|none|600px|Cells and synapses reconstructed from serial block face electron microscopy data. A single starburst amacrine cell (yellow, note synaptic varicosities) and two direction-selective ganglion cells (green). Even though there is substantial dendritic overlap with both cells, all connections (magenta) go to the right ganglion cell. ©Kevin Briggman. [http://www.mpg.de/1200127/direction_selective_ganglion_cells New microscope decodes complex eye circuitry: Retinal ganglion cells can recognise directions thanks to amacrine cells]<ref name="briggman2011">{{cite journal  | author=K. L. Briggman, M. Helmstaedter, and W. Denk|title=€œWiring specificity in the direction-selectivity circuit of the retina|journal=Nature |volume=471|pages=183–188 |year=2011 |doi=10.1038/nature09818}} [[media:10.1038_nature09818.pdf|(PDF Download)]]</ref>]]
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TODO:
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DS ON/OFF ganglion cells receive excitatory input from bipolar cells but also from the previously mentioned starburst cells (Figure 5A), which are also known as cholinergic amacrine cells (Famiglietti, 1983,Masland and Mills, 1979). Besides ACh, starburst amacrine cells (SACs) also release GABA (Brecha et al., 1988,Masland et al., 1984b,Vaney and Young, 1988) and provide DS ganglion cells with inhibition as well (Figure 5A). In addition, the DS ganglion cells receive both GABA and glycinergic inhibition from other amacrine cell types (reviewed in Dacheux et al., 2003).
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[[Image:DSGC_circuitry.jpg|800px]]
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Connections to SAC
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== Molecules ==
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As described above, ON/OFF DS ganglion cells can be divided into 4 subtypes differing in their directional preference, ventral, dorsal, nasal, or temporal. Recent research has identified markers for distinguishing between the different subtypes, and for separating ON/OFF DSGCs from other retinal ganglion cells.  These markers are independent of experience, and suggest a method for how these cells obtain different inputs. 
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The cells of different subtypes also differ in their dendritic structure and synaptic targets in the brain. The neurons that were identified to prefer ventral motion were also found to have dendritic projections in the ventral direction. Also, the neurons that prefer nasal motion had asymmetric dendritic extensions in the nasal direction. Thus, a strong association between the structural and functional asymmetry in ventral and nasal direction was observed. With a distinct property and preference for each subtype, there was an expectation that they could be selectively labeled by molecular markers. The neurons that were preferentially responsive to vertical motion were indeed shown to be selectively expressed by a specific molecular marker. However, molecular markers for other three subtypes have not been yet found <ref name="kay2011">{{cite journal  | author=J. N. Kay, I. D. l. Huerta, I.-J. Kim, Y. Zhang, M. Yamagata, M. W. Chu, M. Meister, and J. R. Sanes|title=€œRetinal ganglion cells with distinct directional preferences differ in molecular identity, structure, and central projections |journal=J. Neurosci. |volume=31|issue=21|pages=7753-7762 |year=2011 |doi=10.1523/​JNEUROSCI.0907-11.2011}} [[media:10.1523_JNEUROSCI.0907-11.2011.pdf‎|(PDF Download)]]</ref>.
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The retina contains ganglion cells (RGCs) that respond selectively to objects moving in particular directions. Individual members of a group ofON-OFF direction-selective RGCs (ooDSGCs) detect stimuli moving in one of four directions: ventral, dorsal, nasal, or temporal. Despite this physiological diversity, little is known about subtype-specific differences in structure, molecular identity,and projections. To seek such differences, we characterized mouse transgenic lines that selectively mark ooDSGCs preferring ventral or nasal motion as well as a line that marks both ventral- and dorsal-preferring subsets. We then used the lines to identify cell surface molecules, including Cadherin 6, CollagenXXV1, and Matrix metalloprotease 17, that are selectively expressed by distinct subsets of ooDSGCs. We also identify a neuropeptide, CART (cocaine- and amphetamine-regulated transcript), that distinguishes all ooDSGCs from other RGCs. Together, this panel of endogenous and transgenic markers distinguishes the four ooDSGC subsets. Patterns of molecular diversification occur before eye opening and are therefore experience independent. They may help to explain how the four subsets obtain distinct inputs. We also demonstrate differences among subsets in their dendritic patterns within the retina and their axonal projections to the brain. Differences in projections indicate that information about motion in different directions is sent to different destinations.
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[[Image:DSGC_circuitry.jpg|thumb|none|800px|Depiction of the circuitry surrounding a ON/OFF DSGC <ref name="borst2011" />]]
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[[File:CARTDSGC.jpg|400px|right|thumb|Figure showing how ON/OFF DSGCs can be distinguished from other RGCs.  As described in the text, this is accomplished using CART; a careful morphological analysis confirms that this marker correctly identifies the ON/OFF DSGCs with no false positives. <ref name="kay2011" />]]
  
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== Molecules == <!--T:11-->
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As described above, ON/OFF DS ganglion cells can be divided into 4 subtypes differing in their directional preference, ventral, dorsal, nasal, or temporal. Recent research has identified markers for distinguishing between the different subtypes, and for separating ON/OFF DSGCs from other retinal ganglion cells.  These markers are independent of experience, and suggest a method for how these cells obtain different inputs.
 +
 
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Recent research has lead to the development of transgenic mouse lines that selectively mark ON/OFF DSGCs that prefer ventral or nasal motion and another line that marks ventral and dorsal preferring DSGCs.  These lines were used to identify cell surface molecules (including Cadherin 6, CollagenXXV1, and Matrix metalloprotease 17), that allow each of the four types of ON/OFF DSGCs to be differentiated.  A neuropeptide, CART (cocaine and amphetamine regulated transcript) has been found to differentiate ON/OFF DSGCs from all other retinal ganglion cells.  Strikingly, these patterns of molecular differentiation occur before animal eye-opening, and demonstrate that these differences are experience-independent.  Therefore, the molecular differences may help to explain the differing functionality between subtypes. <ref name="kay2011">J. N. Kay et al. (2011) Retinal ganglion cells with distinct directional preferences differ in molecular identity, structure, and central projections. J. Neurosci. <strong>31</strong> (21): 7753-7762 doi: [http://dx.doi.org/10.1523/JNEUROSCI.0907-11.2011 10.1523/​JNEUROSCI.0907-11.2011]</ref>
 
== Models ==
 
== Models ==
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The firing pattern of On-Off Direction-Selective Ganglion cells is time-dependent and is supported by the Reichardt- Hassenstain model, which detects spatiotemporal correlation between two adjacent cells <ref name="wiki"></ref>. 
  
The firing pattern of On-Off Direction-Selective Ganglion cells is time-dependent and is supported by the Reichardt- Hassenstain model, which detects spatiotemporal correlation between the two adjacent points <wiki>
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<!--T:12-->
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[[File:Reichardt_model.jpg|thumb|Right|200px|Graphic explaining the Reichardt-Hassenstain model <ref name="wiki" />]]
  
The model consists of two symmetrical subunits. Both subunits have a receptor that can be stimulated by an input (light in the case of visual system). In each subunit, when an input is received, a signal is sent to the other subunit. At the same time, the signal is delayed in time within the subunit, and after the temporal filter, is then multiplied by the signal received from the other subunit. Thus, within each subunit, the two brightness values, one received directly from its receptor with a time delay and the other received from the adjacent receptor, are multiplied. The multiplied values from the two subunits are then subtracted to produce an output.  The direction of selectivity or preferred direction is determined by whether the difference is positive or negative. The direction which produces a positive outcome is the preferred direction.  
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As applied to the visual system, this model considers the processed stimulus(i.e., light) inputs to two adjacent cells. After a time delay, each delayed input is multiplied by the original signal from the other cell. The resulting signals are subtracted, and the positive outcome indicates the preferred direction <ref name="wiki" />.
  
In order to confirm that the Reichardt-Hassenstain model accurately describes the directional selectivity in the retina, the study was conducted using optical recordings of free cytosolic calcium levels after loading a fluorescent indicator dye into the fly tangential cells. The fly was presented uniformly moving gratings while the calcium concentration in the dendritic tips of the tangential cells was measured. The tangential cells showed modulations that matched the temporal frequency of the gratings, and the velocity of the moving gratings at which the neurons respond most strongly showed a close dependency on the pattern wavelength. This confirmed the accuracy of the model both at the cellular and the behavioral level <ref name="hagg2004">{{cite journal  | author=J. Haag|title=€œFly Motion Vision Is Based on Reichardt Detectors Regardless of the Signal-to-noise Ratio |journal=Proc. Natl. Acad. Sci.|volume=101|issue=46|pages=16333-16338 |year=2004 |doi=10.1073/pnas.0407368101}} [[media:10.1073_pnas.0407368101.pdf|(PDF Download)]]</ref>.
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This behavior was validated in the visual system using calcium imaging in the fly <ref name="hagg2004">J. Haag (2004). €œFly Motion Vision Is Based on Reichardt Detectors Regardless of the Signal-to-noise Ratio. Proc. Natl. Acad. Sci. <strong>101</strong> (46): 16333-16338 doi: [http://dx.doi.org/10.1073/pnas.0407368101 10.1073/pnas.0407368101]</ref>. However, this
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model correspondence has only been completed at a high-level (input-output), rather than at an anatomical or physiological level.<ref name="borst2011" />
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== History == <!--T:14-->
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Direction Selective units were first explored in cats by Hubel and Wiesel in 1959.  Levick and Barlow performed many of the seminal early experiments related to direction selectivity during the 1960s using rabbit retina <ref name="barlow1965" />.  In these experiments, they measured action potentials generated from a black-white grating with a small slit <ref name="wiki" />.
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Many additional experiments have been performed during the past fifty years in organisms as diverse as the turtle (e.g., Marchiafava 1979) and the mouse (Briggman 2011).
  
== Development ==  
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== References == <!--T:15-->
  
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<references/>
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{{Retinal Neuron Types}}
  
 
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[[Category:Retinal_Neuron_Types]]
== History ==
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Levick and Barlow performed many of the early experiments related to direction selectivity during the 1960s using rabbit retina <ref name="barlow1965" />.
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Some of the keyfindings in the rabbit retina have been confirmed in the turtle retina (Marchiafava
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1979; Ariel and Adolph 1985; Rosenberg and Ariel 1991; Kittila and Granda
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1994; Smith et al. 1996; Kogo et al. 1998), indicating that similar mechanisms
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may underlie the generation of direction selectivity in diverse vertebrate retinas. In
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the rabbit retina, there are two distinct types of DS ganglion cells <ref name="barlow1965"></ref>(Barlow et al.
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1964). The numerous physiological and morphological studies on vertebrate
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DS ganglion cells have been most recently reviewed by Amthor and Grzywacz
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(1993a), who placed special emphasis on the spatiotemporal characteristics of the
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excitatory and inhibitory inputs to the On-Off DS cells.
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Although the actual neuronal circuitry that underlies the generation of direction selectivity in the retina has yet to be elucidated, the diverse models that have been proposed over the last 35 years provide guideposts for future experiments (Barlow and Levick 1965; Torre and Poggio 1978; Ariel and Daw 1982; Koch et al. 1982; Grzywacz and Amthor 1989; Vaney et al. 1989; Oyster 1990; Vaney 1990; Borg-Graham and Grzywacz 1992; Grzywacz et al. 1997; Kittila and Massey 1997). These models are judged primarily by their ability to account for
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the detailed functional properties of the DS ganglion cells, but this is only one of the requirements. Morphological and biophysical constraints also pose hurdles for candidate mechanisms. For example, it would not be appropriate to require a
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higher density of a particular neuronal type than is known to exist. Nor would it be sound to postulate highly localised synaptic interactions on dendritic segments where the electrotonic properties indicate more extensive interactions. Finally, the developmental requirements need to be kept in mind: it should be possible to achieve the appropriate specificity in the neuronal connections by such mechanisms as Hebbian-type synaptic modification or the selective expression of marker molecules
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== Open questions / status / relevance to eyewire ==
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Cells are available for tracing in Eyewire, although these cells are not currently available (March 2012).
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See http://wiki.eyewire.org/wiki/E2198
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== Reading List ==
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K. L. Briggman, M. Helmstaedter, and W. Denk, €œWiring specificity in the direction-selectivity circuit of the retina., Nature, vol. 471, no. 7337, pp. 183-8, Mar. 2011.
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A. Borst and T. Euler, €œReview Seeing Things in Motion : Models, Circuits and Mechanisms,€ Neuron, vol. 71, no. 6, pp. 974-994, 2011.
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D. I. Vaney, B. Sivyer, and W. R. Taylor, Direction selectivity in the retina: symmetry and asymmetry in structure and function,€ Nature reviews. Neuroscience, vol. 13,  no. 3, pp. 194-208, Jan. 2012.
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W. R. Levick and H. B. Barlow, €œThe Mechanism of Directionally Selective Units in Rabbit's Retina, pp. 477-504, 1965.
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== References ==
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<references/>
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Latest revision as of 03:55, 20 July 2019

an ON-OFF direction-selective ganglion cell reconstructed in EyeWire

Direction selective (DS) cells in the retina are neurons that respond differentially to the direction of a visual stimulus. The term is used to describe a group of neurons that preferentially "gives a vigorous discharge of impulses when a stimulus is moved through its receptive field in one direction." [1] There are three known types of DS cells in the vertebrate retina of the mouse, ON/OFF DS Ganglion Cells, ON DS Ganglion Cells (which respond to the leading edge of a bright stimulus) and OFF DS Ganglion Cells (which respond only to the trailing edge of a bright stimulus). Each has a distinctive physiology and anatomy.[2] The rest of this page will only apply to ON/OFF DS Ganglion Cells.

Physiology

Diagram showing the response of ON/OFF DSGC to stimulus in the null and preferred direction. Inputs are multiplied in the preferred direction, and suppressed in the null direction.[3]

ON/OFF DSGCs act as local motion detectors. If a bright stimulus (e.g., a light) is moving in the direction of the cell's preference, the cell will fire at both the leading and trailing edge. An important contrast is that bright stimuli moving opposite the preferred direction (called the null direction), elicit little or no response [2]. The response to stimulus is independent of many stimulus properties, including size, shape, color, and speed. These cells have a center-surround structure, and the size of the dendrite correlates with the size of the center receptive field. [1]

ON/OFF DSGCs can be divided into 4 subtypes differing in their directional preference, ventral, dorsal, nasal, or temporal. The cells of different subtypes also differ in their dendritic structure and synaptic targets in the brain.[4]

From the early experiments in the 1960s, it was shown that receptive fields are fairly large, sensitive to small changes, and direction-selective subunits are repeated many times throughout the retina.[1]

Anatomy

Error creating thumbnail: Unable to save thumbnail to destination
Image of an On-Off Direction-Selective Ganglion Cell[5].

The ON/OFF DSGCs are commonly recognized by their bistratified dendritic arbors, which extend to two layers of the inner plexiform layer (IPL). These cell types are also known to synapse with both bipolar cells and starburst amacrine cells (SAC). As described above, there are four cell subtypes, each with own preference for direction. Each subtype of ON/OFF DSGCs has differences in dendritic patterns and axonal projections to the brain. These differences indicate that outputs from different subtypes may wire to different parts of the brain [4]

Depiction of six reconstructed ON/OFFDSGCs. Figure A shows the bistratification of the ON and OFF arbors. Colors correspond to orientation of preferred direction. Figure B shows a bottom view of the traced arbors.[6]

Connections

Excitation comes from both bipolar cells and starburst amacrine cells.[5] The main source of inhibition is from starburst amacrine cells. Using manual reconstruction of 6 ON/OFF DSGCs and their synaptic partners, it was found that over 90% of SAC – ON/OFF DSGC synapses were oriented in the null direction.[6]

As illustrated in the accompanying figure, light enters the retina through the photoreceptors, and excitatory inputs are transmitted to the ON/OFF DSGCs via Glutamate and Acetylcholine from the bipolar and starburst amacrine cells. Inhibitory GABA inputs, which are crucial for suppressing information in the null direction (and thereby creating a direction-selective motion detector) are received from SACs. The motion detection result is fed to higher parts of the brain for further processing.

Error creating thumbnail: Unable to save thumbnail to destination
Depiction of the circuitry surrounding a ON/OFF DSGC [5]
Error creating thumbnail: Unable to save thumbnail to destination
Figure showing how ON/OFF DSGCs can be distinguished from other RGCs. As described in the text, this is accomplished using CART; a careful morphological analysis confirms that this marker correctly identifies the ON/OFF DSGCs with no false positives. [4]

Molecules

As described above, ON/OFF DS ganglion cells can be divided into 4 subtypes differing in their directional preference, ventral, dorsal, nasal, or temporal. Recent research has identified markers for distinguishing between the different subtypes, and for separating ON/OFF DSGCs from other retinal ganglion cells. These markers are independent of experience, and suggest a method for how these cells obtain different inputs.

Recent research has lead to the development of transgenic mouse lines that selectively mark ON/OFF DSGCs that prefer ventral or nasal motion and another line that marks ventral and dorsal preferring DSGCs. These lines were used to identify cell surface molecules (including Cadherin 6, CollagenXXV1, and Matrix metalloprotease 17), that allow each of the four types of ON/OFF DSGCs to be differentiated. A neuropeptide, CART (cocaine and amphetamine regulated transcript) has been found to differentiate ON/OFF DSGCs from all other retinal ganglion cells. Strikingly, these patterns of molecular differentiation occur before animal eye-opening, and demonstrate that these differences are experience-independent. Therefore, the molecular differences may help to explain the differing functionality between subtypes. [4]

Models

The firing pattern of On-Off Direction-Selective Ganglion cells is time-dependent and is supported by the Reichardt- Hassenstain model, which detects spatiotemporal correlation between two adjacent cells [2].

File:Reichardt model.jpg
Graphic explaining the Reichardt-Hassenstain model [2]

As applied to the visual system, this model considers the processed stimulus(i.e., light) inputs to two adjacent cells. After a time delay, each delayed input is multiplied by the original signal from the other cell. The resulting signals are subtracted, and the positive outcome indicates the preferred direction [2].

This behavior was validated in the visual system using calcium imaging in the fly [7]. However, this model correspondence has only been completed at a high-level (input-output), rather than at an anatomical or physiological level.[5]

History

Direction Selective units were first explored in cats by Hubel and Wiesel in 1959. Levick and Barlow performed many of the seminal early experiments related to direction selectivity during the 1960s using rabbit retina [1]. In these experiments, they measured action potentials generated from a black-white grating with a small slit [2]. Many additional experiments have been performed during the past fifty years in organisms as diverse as the turtle (e.g., Marchiafava 1979) and the mouse (Briggman 2011).

References

  1. 1.0 1.1 1.2 1.3 H. B. Barlow and W. R. Levick (1965) The Mechanism of Directionally Selective Units in Rabbit's Retina J. Physiol. 178: 477-504
  2. 2.0 2.1 2.2 2.3 2.4 2.5 "Motion Sensing in Vision." Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/wiki/Motion_Sensing_in_Vision (Accessed April 02, 2012).
  3. D. I. Vaney, B. Sivyer, and W. R. Taylor (2012). Direction selectivity in the retina: symmetry and asymmetry in structure and function. Nature Neuroscience 13 (3): 194-208
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